Neoadjuvant targeted immunotherapy followed by surgical resection versus upfront surgery for hepatocellular carcinoma with macrovascular invasion: A multicenter study.

Background: This study aimed to investigate the safety and efficacy of preoperative targeted immunotherapy followed by surgical resection for hepatocellular carcinoma (HCC) patients with macrovascular invasion. Method: Clinical information of HCC patients with macrovascular invasion was collected from four medical centers. These patients were divided into two cohorts: the upfront surgery group (n=40) and the neoadjuvant group (n=22). Comparisons between the two groups were made with appropriate statistical methods. Results: HCC Patients with macrovascular invasion in the neoadjuvant group were associated with increased incidence of postoperative ascites (72.73% vs. 37.5%, P=0.008), but shorter postoperative hospital stay (10 days vs. 14 days, P=0.032). Furthermore, targeted immunotherapy followed by surgical resection significantly reduced the postoperative recurrence rate at both 3 months and 1 year (9% versus 28.9%, 32.1% versus 67.9%, respectively; P=0.018), but increased the postoperative nononcologic mortality rate within 1 year (20.1% vs. 2.8%; P= 0.036). Conclusion: For HCC patients with macrovascular invasion, preoperative targeted immunotherapy significantly decreased the postoperative tumor recurrence rate while maintaining relative safety, but such a treatment may also result in chronic liver damage and increased risk of nononcologic mortality.

Conversion surgery intervention versus continued systemic therapy in patients with a response after PD-1/PD-L1 inhibitor-based combination therapy for initially unresectable biliary tract cancer: a retrospective cohort study.

BACKGROUND: The role of conversion surgery in patients with unresectable biliary tract cancer (BTC) who responded positively to PD-1/PD-L1 inhibitor-based therapy remains unclear. This study aimed to assess the outcomes in patients with or without conversion surgery. METHODS: In this cohort study, patients with advanced BTC who received combination therapy with PD-1/PD-L1 inhibitors from July 2019 to January 2023 were retrospectively. Patients who exhibited positive responses and met the criteria for conversion surgery were enrolled, and their surgical and oncological outcomes were analyzed. RESULTS: Out of 475 patients, 34 who met the conversion resection criteria were enrolled. The median follow-up was 40.5 months post-initiation of systemic therapy. Ultimately, 13 patients underwent conversion surgery, while 21 received continuation of systemic treatment alone (non-surgical group). The median interval from the initial antitumor therapy to surgery was 6.7 (interquartile range [IQR] 4.9-9.2) months. Survival with conversion surgery was significantly longer than the non-surgical cohort, with a median progression-free survival (PFS) (unreached vs. 12.4 mo; hazard ratio 0.17 [95% CI 0.06-0.48]; P=0.001) and overall survival (OS) (unreached vs. 22.4 mo; hazard ratio 0.28 [95% CI 0.09-0.84]; P=0.02), respectively. After a median postoperative follow-up of 32.2 months in the surgical cohort, 8 patients survived without recurrence. The estimated 3-year OS, PFS and recurrence-free survival rate in the surgical cohort were 59.9%, 59.2% and 60.6%, respectively. The R0 resection rate reached 92.3%, with 2 achieving a pathological complete response. One patient experienced a Clavien-Dindo grade 3 complication without surgery-related mortality. No serious adverse events or surgical delays were observed. Multivariate analysis indicated that conversion surgery was independently associated with OS (P=0.03) and PFS survival (P=0.003). CONCLUSION: Conversion surgery appears safe and offers survival benefits to patients responding to immune checkpoint inhibitors (ICIs)-based combinations. However, further studies are required to validate this strategy in the era of immunotherapy.

Development and validation of web-based nomograms for predicting survival status in patients with intrahepatic cholangiocarcinoma depending on the surgical status: a SEER database analysis.

This study aimed to develop and validate prognostic nomograms that can estimate the probability of 1-, 3- and 5-year overall survival (OS) as well as cancer-specific survival (CSS) for Intrahepatic cholangiocarcinoma (ICCA) patients. Clinical data of 1446 patients diagnosed with ICCA between 2010 and 2017 from the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. In both the OS and the CSS group, the training cohort and validation cohort were divided into a 7:3 ratio. Age, sex, AJCC T stage, AJCC N stage, AJCC M stage, surgical status, and tumor grade were selected as independent prognostic risk factors to build the nomograms. To compare the efficacy of predicting 1-, 3-, and 5-year OS and CSS rates of the nomogram with the 8th edition of the American Joint Committee on Cancer (AJCC) staging system, we evaluated the Harrell's index of concordance (C-index), area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) in both cohorts. The results showed the nomogram for 1-, 3-, and 5-year OS and CSS prediction performed better than the AJCC staging system. In the subgroup analysis for patients could not receive surgery as the primary treatment. We developed two nomograms for predicting the 1-, and 2-year OS and CSS rates following the same analysis procedure. Results indicate that the performance of both nomograms, which contained sex, AJCC T stage, AJCC M stage, chemotherapy, and tumor grade and prognostic factors, was also superior to the AJCC staging system. Meanwhile, four dynamic network-based nomograms were published. The survival analysis showed the survival rate of patients classified as high-risk based on the nomogram score was significantly lower compared to those categorized as low-risk (P < 0.0001). Finally, accurate and convenient nomograms were established to assist clinicians in making more personalized prognosis predictions for ICCA patients.

Worldwide research trends on tumor burden and immunotherapy: a bibliometric analysis.

Various immunotherapy has been greatly applied to comprehensive treatment of malignant cancer under different degrees of tumor burden. Scientific researchers have gained considerable progress in the relationship between immunotherapy and tumor burden in recent years. This review aimed to explore the prospect and developing trends in the field of tumor burden and immunotherapy from a bibliometric perspective. Articles about tumor burden and immunotherapy were collected from the Web of Science Core Collection (WoSCC) (retrieved on 3 January 2023). The R package 'Bibliometrix' analyzed the primary bibliometric features and created a three-filed plot to display the relationship between institutions, countries, and keywords. VOSviewer was used for co-authorship analysis, co-occurrence analysis, and their visualization. And CiteSpace calculated the citation burst references and keywords. A total of 1030 publications were retrieved from 35 years of scientific researches. The United States (US) and China published the most articles. The most productive journals were Cancer Immunology Immunotherapy and Journal for ImmunoTherapy of Cancer . The top one institution of the highest output was University of Texas MD Anderson Cancer Center. The hot keywords of strong citation burst strength in recent years were 'nivolumab', 'tumor microenvironment', and 'immune checkpoint inhibitor'. The most popular tumor type is melanoma. This bibliometric analysis mapped a basic knowledge structure. The field of tumor burden and immunotherapy is entering a rapid growing stage and keeping it value for future research.

Genomic characterization and immunotherapy for microsatellite instability-high in cholangiocarcinoma.

BACKGROUND: Microsatellite instability-high (MSI-H) is a unique genomic status in many cancers. However, its role in the genomic features and immunotherapy in cholangiocarcinoma (CCA) is unclear. This study aimed to systematically investigate the genomic characterization and immunotherapy efficacy of MSI-H patients with CCA. METHODS: We enrolled 887 patients with CCA in this study. Tumor samples were collected for next-generation sequencing. Differences in genomic alterations between the MSI-H and microsatellite stability (MSS) groups were analyzed. We also investigated the survival of PD-1 inhibitor-based immunotherapy between two groups of 139 patients with advanced CCA. RESULTS: Differential genetic alterations between the MSI-H and MSS groups included mutations in ARID1A, ACVR2A, TGFBR2, KMT2D, RNF43, and PBRM1 which were enriched in MSI-H groups. Patients with an MSI-H status have a significantly higher tumor mutation burden (TMB) (median 41.7 vs. 3.1 muts/Mb, P < 0.001) and more positive programmed death ligand 1 (PD-L1) expression (37.5% vs. 11.9%, P < 0.001) than those with an MSS status. Among patients receiving PD-1 inhibitor-based therapy, those with MSI-H had a longer median overall survival (OS, hazard ratio (HR) = 0.17, P = 0.001) and progression-free survival (PFS, HR = 0.14, P < 0.001) than patients with MSS. Integrating MSI-H and PD-L1 expression status (combined positive score ≥ 5) could distinguish the efficacy of immunotherapy. CONCLUSIONS: MSI-H status was associated with a higher TMB value and more positive PD-L1 expression in CCA tumors. Moreover, in patients with advanced CCA who received PD-1 inhibitor-based immunotherapy, MSI-H and positive PD-L1 expression were associated with improved both OS and PFS. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov on 07/01/2017 (NCT03892577).

Prediction of Clinical Precision Chemotherapy by Patient-Derived 3D Bioprinting Models of Colorectal Cancer and Its Liver Metastases.

Methods accurately predicting the responses of colorectal cancer (CRC) and colorectal cancer liver metastasis (CRLM) to personalized chemotherapy remain limited due to tumor heterogeneity. This study introduces an innovative patient-derived CRC and CRLM tumor model for preclinical investigation, utilizing 3d-bioprinting (3DP) technology. Efficient construction of homogeneous in vitro 3D models of CRC/CRLM is achieved through the application of patient-derived primary tumor cells and 3D bioprinting with bioink. Genomic and histological analyses affirm that the CRC/CRLM 3DP tumor models effectively retain parental tumor biomarkers and mutation profiles. In vitro tests evaluating chemotherapeutic drug sensitivities reveal substantial tumor heterogeneity in chemotherapy responses within the 3DP CRC/CRLM models. Furthermore, a robust correlation is evident between the drug response in the CRLM 3DP model and the clinical outcomes of neoadjuvant chemotherapy. These findings imply a significant potential for the application of patient-derived 3DP cancer models in precision chemotherapy prediction and preclinical research for CRC/CRLM.

Radiation Therapy With Combination Therapy of Immune Checkpoint Inhibitors and Antiangiogenic Therapy for Hepatocellular Carcinoma.

PURPOSE: Immune checkpoint inhibitors (ICIs) combined with antiangiogenic therapy have limited efficacy in treating advanced hepatocellular carcinoma (HCC). The synergistic effect of systemic therapy and radiation therapy (RT) might resolve this problem. We aimed to investigate the effect of RT on the treatment outcomes of ICIs and antiangiogenic combination therapy in patients with advanced-stage HCC. METHODS AND MATERIALS: This retrospective observational study analyzed the medical records of 194 patients with Barcelona Clinic Liver Cancer stage C HCC who were admitted to our center from August 2018 to June 2022 and received ICIs combined with antiangiogenic therapy as the first-line treatment. Patients who were administered RT for tumor thrombus or symptomatic metastases within 8 weeks of the commencement of combination therapy were allocated to the RT group, whereas those who did not receive RT were assigned to the non-radiation therapy (NRT) group. Propensity score matching was used to mitigate selection bias. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints included objective response rate, disease control rate (DCR), local PFS, out-of-field PFS, and treatment-related adverse events. RESULTS: A total of 76 patients diagnosed with advanced-stage HCC and treated with ICIs and antiangiogenic therapy were included in the study, with 33 patients in the RT group and 43 patients in the non-RT group. After propensity score matching, 29 matched patient pairs were generated. The median follow-up was 15.5 months, and the RT sites were mainly located on the tumor thrombus (55.2%) and extrahepatic metastatic lesions (48.3%). The median PFS was 8.3 months (95% CI, 5.4-11.3) in the RT group and 4.2 months (95% CI, 3.4-5.0) in the NRT group (P < .001). The median OS was not reached in the RT group and was 9.7 months (95% CI, 4.1-15.3) in the NRT group (P = .002). The objective response rate was 75.9% (95% CI, 56.5-89.7) in the RT group and 24.1% (95% CI, 10.3-43.5) in the NRT group (P < .001). The DCR was 100% in the RT group and 75.9% (95% CI, 56.5-89.7) in the NRT group (P = .005). The median local PFS and out-of-field PFS were 13.2 months (95% CI, 6.3-20.1) and 10.8 months (95% CI, 7.0-14.7), respectively. RT was an independent prognostic factor for PFS (hazard ratio = 0.33; 95% CI, 0.17-0.64; P < .001) and OS (hazard ratio = 0.28; 95% CI, 0.11-0.68; P = .005), respectively. The rates of any grade treatment-related adverse events were similar between the 2 groups. CONCLUSIONS: In comparison to the combination of ICIs and antiangiogenic therapy, the inclusion of RT has been observed to improve the DCR and survival outcomes in patients with advanced-stage HCC. The safety profile of this triple therapy was satisfactory.

Efficacy and safety of subsequent radiotherapy in patients with advanced-stage hepatocellular carcinoma treated with immune checkpoint inhibitors.

Background: The development of immunotherapy resistance is associated with a poor prognosis in patients diagnosed with hepatocellular carcinoma (HCC) who are undergoing treatment with immune checkpoint inhibitors (ICI). This study aimed to evaluate the efficacy and safety of subsequent radiotherapy (RT) for patients with advanced-stage HCC who had lesion enlargement or new lesions (NLs) during ICI therapy. Methods: This retrospective observational study enrolled 36 patients with advanced-stage HCC who underwent subsequent RT for lesion enlargement or NLs during ICI therapy from two centers. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), 1- and 2-year local control (LC) rates, in-field PFS (IFPFS), out-field PFS (OFPFS), and safety. Results: The median follow-up time was 15.3 months. The median PFS was 7.4 months [95% confidence interval (CI): 3.1-11.7 months], and the median OS was 18.8 months (95% CI: 17.1-20.5 months). ORR and DCR were 38.9% and 72.2%, respectively. In addition, the median IFPFS was 17.8 months (95% CI: 11.5-24.2 months), median OFPFS was 7.9 months (95% CI: 3.4-12.5 months), and estimated 1- and 2-year LC rates were 67.1% and 31.9%, respectively. The most common treatment-related adverse events (all grades) were diarrhea (33.3%), rash (30.6%), and malaise (27.8%); a total of 14 (38.9%) patients developed grade 3-4 AEs. Conclusions: Subsequent RT showed reliable antitumor effects and an acceptable safety profile in patients with advanced-stage HCC who had unsatisfactory response to ICI therapy; therefore, it could serve as an optional salvage strategy.

Immune checkpoint inhibitor-related molecular markers predict prognosis in extrahepatic cholangiocarcinoma.

BACKGROUND: Therapeutic approaches for extrahepatic cholangiocarcinoma (EHCC) are limited, due to insufficient understanding to biomarkers related to prognosis and drug response. Here, we comprehensively assess the molecular characterization of EHCC with clinical implications. METHODS: Whole-exome sequencing (WES) on 37 tissue samples of EHCC were performed to evaluate genomic alterations, tumor mutational burden (TMB) and microsatellite instability (MSI). RESULTS: Mutation of KRAS (16%) was significantly correlated to poor OS. ERBB2 mutation was associated with improved OS. ERBB2, KRAS, and ARID1A were three potentially actionable targets. TMB ≥10 mutations per megabase was detected in 13 (35.1%) cases. Six patients (16.2%) with MSIsensor scores ≥10 were found. In multivariate Cox analysis, patients with MSIsensor sore exceed a certain threshold (MSIsensor score ≥0.36, value approximately above the 20th percentile as thresholds) showed a significant association with the improved OS (HR = 0.16; 95% CI: 0.056-0.46, p < 0.001), as well as patients with both TMB ≥3.47 mutations per megabase (value approximately above the 20th percentile) and MSIsensor score ≥0.36. CONCLUSIONS: TMB and MSI are potential biomarkers associated with better prognosis for EHCC patients. Furthermore, our study highlights important genetic alteration and potential therapeutic targets in EHCC.

Urinary biomarkers for hepatocellular carcinoma: current knowledge for clinicians.

Hepatocellular carcinoma (HCC) is the most predominant primary liver cancer, causing many illnesses and deaths worldwide. The insidious clinical presentation, difficulty in early diagnosis, and the highly malignant nature make the prognosis of HCC extremely poor. The complex and heterogeneous pathogenesis of HCC poses significant challenges to developing therapies. Urine-based biomarkers for HCC, including diagnostic, prognostic, and monitoring markers, may be valuable supplements to current tools such as serum α-fetoprotein (AFP) and seem promising for progress in precision medicine. Herein, we reviewed the major urinary biomarkers for HCC and assessed their potential for clinical application. Molecular types, testing platforms, and methods for building multimolecule models in the included studies have shown great diversity, thus providing abundant novel tools for future clinical transformation and applications.

Unravelling the liver-brain connection: A two-sample Mendelian randomization study investigating the causal relationship between NAFLD and cortical structure.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been linked to cognitive decline and neuropsychiatric conditions, implying a potential connection between NAFLD and brain health. However, the causal association between NAFLD and cortical changes remains uncertain. This study aimed to examine the causal impact of NAFLD on cortical structures using a two-sample Mendelian randomization (MR) approach. METHODS: Summary data from genome-wide association studies (GWAS) for NAFLD were gathered from large-scale cohorts. Surface area (SA) and cortical thickness (TH) measurements were derived from Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium magnetic resonance imaging (MRI) data of 33,992 participants. Inverse-variance weighted (IVW) served as the primary method. Additional sensitivity analyses, including MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), MR-Egger, and weighted median procedures, were conducted to detect heterogeneity and pleiotropy. RESULTS: Our MR analysis revealed that NAFLD led to notable alterations in cortical structures, particularly in the pars orbitalis gyrus. Specifically, genetically predicted NAFLD was linked to a decrease in TH (ß = -0.008 mm, 95 % CI: -0.013 mm to -0.004 mm, P = 3.00 × 10-4) within this region. No significant heterogeneity and pleiotropy were identified. CONCLUSION: The two-sample MR study supports the existence of a liver-brain axis by demonstrating a causal association between NAFLD and changes in cortical structures. These findings emphasize the potential association between NAFLD and brain health, which could have implications for preventing and treating cognitive deficits and neuropsychiatric conditions in patients with NAFLD.

The effects of intermittent bolus paravertebral block on analgesia and recovery in open hepatectomy: a randomized, double-blinded, controlled study.

BACKGROUND: We aimed to investigate the effects of intermittent bolus paravertebral block on analgesia and recovery in open hepatectomy. METHODS: Eighty 18-70 years old, American Society of Anesthesiologists level I-III patients scheduled for hepatectomy with a J-shaped subcostal incision were enrolled and randomized to receive either intermittent bolus paravertebral ropivacaine (0.5% loading, 0.2% infusion) or 0.9% saline infusion at 1:1 ratio (25 ml loading before surgery, 0.125 ml/kg/h bolus for postoperative 48 h). The primary outcome was set as postoperative 48 h cumulative intravenous morphine consumption recorded by a patient-controlled analgesic pump. RESULTS: Thirty-eight patients in each group completed the study. The cumulative morphine consumptions were lower in the paravertebral block than control group at postoperative 24 (difference -10.5 mg, 95%CI -16 mg to -6 mg, P < 0.001) and 48 (difference -12 mg, 95%CI -19.5 mg to -5 mg, P = 0.001) hours. The pain numerical rating scales at rest were lower in the paravertebral block than control group at postoperative 4 h (difference -2, 95%CI -3 to -1, P < 0.001). The active pain numerical rating scales were lower in the paravertebral block than control group at postoperative 12 h (difference -1, 95%CI -2 to 0, P = 0.005). Three months postoperatively, the paravertebral block group had lower rates of hypoesthesia (OR 0.28, 95%CI 0.11 to 0.75, P = 0.009) and numbness (OR 0.26, 95%CI 0.07 to 0.88, P = 0.024) than the control group. CONCLUSIONS: Intermittent bolus paravertebral block provided an opioid-sparing effect and enhanced recovery both in hospital and after discharge in patients undergoing hepatectomy. TRIAL REGISTRATION: clinicaltrials.gov (NCT04304274), date: 11/03/2020.

Intratumoural microbiome can predict the prognosis of hepatocellular carcinoma after surgery.

BACKGROUND: The dismal prognosis of hepatocellular carcinoma (HCC) is closely associated with characteristics of the tumour microenvironment (TME). Recent studies have confirmed the presence and potential influence of the microbiome in TME on cancer progression. Elucidating the relationship between microbes in the TME and cancer could provide valuable insights into novel diagnostic markers and therapeutic strategies for HCC and thus warrants a closer investigation of the role of intratumoural microbiome in the HCC TME. METHODS: We determined the presence of intratumoural microbiome using fluorescence in situ hybridisation, and explored the microbial community profiles in the HCC TME in paired tumour and adjacent normal tissues using 16S rDNA sequencing. Microbial signatures were characterised in the paired group, and their correlation with clinical characteristics was further investigated. We clustered the microbial signatures of tumour tissues by hepatotypes, and further analysis was performed to elucidate the independent prognostic value of the hepatotypes. RESULTS: This study revealed that microbial profiles and community networks differed notably between tumours and adjacent normal tissues. Proteobacteria and Actinobacteria were the most abundant phyla in the HCC TME. The TME microbial profiles also revealed heterogeneities between individuals and between multiple tumour lesions. Clustering of the microbial profiles into two hepatotypes revealed different microbial network patterns. Additionally, the hepatotypes were revealed to be independent prognostic factors in patients with resected HCC. CONCLUSIONS: Our study illuminates the microbial profiles in the TME of HCC and presents the hepatotype as a potential independent biomarker for the prognostic prediction of HCC after surgery.

Comparison of Baseline 68Ga-FAPI and 18F-FDG PET/CT for Prediction of Response and Clinical Outcome in Patients with Unresectable Hepatocellular Carcinoma Treated with PD-1 Inhibitor and Lenvatinib.

Fibroblast activation protein contributes to immunosuppression and resistance to immunotherapies. This study aimed to compare baseline 68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI) PET/CT and 18F-FDG PET/CT in response and survival prediction in unresectable hepatocellular carcinoma (uHCC) patients treated with the combination of programmed cell death 1 (PD-1) inhibitor and lenvatinib. Methods: In this prospective cohort study, 22 patients with uHCC who underwent baseline 18F-FDG and 68Ga-FAPI PET/CT and soon began taking a combination of PD-1 inhibitor and lenvatinib were recruited. Semiquantitative indices of baseline PET/CT were measured as 18F-FDG SUVmax, metabolic tumor volume, total lesion glycolysis, 68Ga-FAPI SUVmax, 68Ga-FAPI-avid tumor volume (FTV), and total lesion fibroblast activation protein expression (TLF). The primary endpoint was durable or nondurable clinical benefit after treatment, and the secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results: The overall response rate of the combination therapy was 41% (9/22). Fifty percent of patients had durable clinical benefit. Median PFS and OS were 4.8 and 14.4 mo, respectively. Patients with nondurable clinical benefit showed a significantly higher FTV and TLF than those with durable clinical benefit, whereas 18F-FDG parameters overlapped. A higher 68Ga-FAPI-avid tumor burden (FTV > 230.46 cm3 or TLF > 961.74 SUVbody weight⋅cm3) predicted both shorter PFS (4.0 vs. 13.5 mo, P = 0.016) and shorter OS (7.8 mo vs. not reached, P = 0.030). Patients with a higher metabolic tumor burden (metabolic tumor volume > 206.80 cm3 or total lesion glycolysis > 693.53 SUVbody weight⋅cm3) showed a shorter OS although the difference did not reach statistical significance (P = 0.085). In multivariate analysis, a higher 68Ga-FAPI-avid tumor burden (hazard ratio [HR], 3.88 [95% CI, 1.26-12.01]; P = 0.020) and macrovascular invasion (HR, 4.00 [95% CI, 1.06-15.14]; P = 0.039) independently predicted a shorter PFS, whereas a higher 68Ga-FAPI-avid tumor burden (HR, 5.92 [95% CI, 1.19-29.42]; P = 0.035) and bone metastases (HR, 5.88 [95% CI, 1.33-25.93]; P = 0.022) independently predicted a shorter OS. Conclusion: Volumetric indices on baseline 68Ga-FAPI PET/CT were potentially independent prognostic factors to predict durable clinical benefit, PFS, and OS in uHCC patients treated with a combination of PD-1 and lenvatinib. Baseline 68Ga-FAPI PET/CT may facilitate uHCC patient selection before combination therapy.

Worldwide productivity and research trend of publications concerning tumor immune microenvironment (TIME): a bibliometric study.

BACKGROUND: As the complexity and diversity of the tumor immune microenvironment (TIME) are becoming better understood, burgeoning research has progressed in this field. However, there is a scarcity of literature specifically focused on the bibliometric analysis of this topic. This study sought to investigate the development pattern of TIME-related research from 2006 to September 14, 2022, from a bibliometric perspective. METHODS: We acquired both articles and reviews related to TIME from the Web of Science Core Collection (WoSCC) (retrieved on September 14, 2022). R package "Bibliometrix" was used to calculate the basic bibliometric features, present the collaborative conditions of countries and authors, and generate a three-field plot to show the relationships among authors, affiliations, and keywords. VOSviewer was utilized for co-authorship analysis of country and institution and keyword co-occurrence analysis. CiteSpace was used for citation burst analysis of keywords and cited references. In addition, Microsoft Office Excel 2019 was used to develop an exponential model to fit the cumulative publication numbers. RESULTS: A total of 2545 publications on TIME were included, and the annual publication trend exhibited a significant increase over time. China and Fudan University were the most productive country and institution, with the highest number of publications of 1495 and 396, respectively. Frontiers in Oncology held the highest number of publications. A number of authors were recognized as the main contributors in this field. The clustering analysis revealed six clusters of keywords that highlighted the research hot spots in the fields of basic medical research, immunotherapy, and various cancer types separately. CONCLUSIONS: This research analyzed 16 years of TIME-related research and sketched out a basic knowledge framework that includes publications, countries, journals, authors, institutions, and keywords. The finding revealed that the current research hot spots of the TIME domain lie in "TIME and cancer prognosis", "cancer immunotherapy", and "immune checkpoint". Our researchers identified the following areas: "immune checkpoint-based immunotherapy", "precise immunotherapy" and "immunocyte pattern", which may emerge as frontiers and focal points in the upcoming years, offering valuable avenues for further exploration.

Pancreatic ductal adenocarcinoma with synchronous and metachronous hepatic metastasis predicted by contrast-enhanced ultrasound.

Background: Contrast-enhanced ultrasound (CEUS) has proven valuable in diagnosing benign and malignant pancreatic diseases, but its value in evaluating hepatic metastasis remains to be further explored. This study investigated the relationship between CEUS features of pancreatic ductal adenocarcinoma (PDAC) and concomitant or recurrent liver metastases after treatment. Methods: This retrospective study included 133 participants with PDAC who were diagnosed with pancreatic lesions with CEUS at Peking Union Medical College Hospital from January 2017 to November 2020. According to the CEUS classification methods in our center, all the pancreatic lesions were classified as either with rich or poor blood supply. Additionally, quantitative ultrasonographic parameters were measured in the center and periphery of all pancreatic lesions. CEUS modes and parameters of the different hepatic metastasis groups were compared. The diagnostic performance of CEUS was calculated for diagnosing synchronous and metachronous hepatic metastasis. Results: The proportions of rich blood supply and poor blood supply were 46% (32/69) and 54% (37/69), respectively, in the no hepatic metastasis group; 42% (14/33) and 58% (19/33), respectively, in the metachronous hepatic metastasis (MHM) group; and 19% (6/31) and 81% (25/31), respectively, in the synchronous hepatic metastasis (SHM) group. The wash-in slope ratio (WIS ratio) between the center of the lesion and around the lesion and peak intensity ratio (PI ratio) between the center of the lesion and around the lesion had higher values in the negative hepatic metastasis group (P<0.05). In predicting synchronous and metachronous hepatic metastasis, the WIS ratio had the best diagnostic performance. The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) were 81.8%, 95.7%, 91.2%, 90.0%, and 91.7%, respectively, for MHM; and 87.1%, 95.7%, 93.0%, 90.0%, and 94.3%, respectively, for SHM. Conclusions: CEUS would be helpful in image surveillance for synchronous or metachronous hepatic metastasis of PDAC.

Efficacy, safety, and prognostic factors of PD-1 inhibitors combined with lenvatinib and Gemox chemotherapy as first-line treatment in advanced intrahepatic cholangiocarcinoma: a multicenter real-world study.

BACKGROUND: A programmed cell death protein-1 (PD-1) inhibitor combined with lenvatinib and Gemox chemotherapy as first-line therapy demonstrated high anti-tumor activity against biliary tract cancer in phase II clinical trials. Herein, we aimed to investigate the efficacy and safety for advanced intrahepatic cholangiocarcinoma (ICC) in a multicenter real-world study. METHODS: Patients with advanced ICC who received PD-1 inhibitor combined with lenvatinib and Gemox chemotherapy were retrospectively screened at two medical centers. The primary endpoints were overall survival (OS) and progression-free survival (PFS), whereas the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and safety. Prognostic factors for survival were analyzed. RESULTS: Fifty-three patients with advanced ICC were included in this study. The median follow-up time was 13.7 (95% confidence interval (CI): 12.9-17.2) months. The median OS and PFS were 14.3 (95% CI: 11.3-NR) and 8.63 (95% CI: 7.17-11.6) months, respectively. The ORR, DCR, and clinical benefit rate were 52.8, 94.3, and 75.5%, respectively. In the multivariate analysis, the tumor burden score (TBS), tumor-node metastasis classification (TNM) stage, and PD-L1 expression were independent prognostic factors for OS and PFS. All patients experienced adverse events (AEs), 41.5% (22/53) experienced grade 3 or 4 AEs, including fatigue (8/53, 15.1%) and myelosuppression (7/53, 13.2%). No grade 5 AEs were reported. CONCLUSION: PD-1 inhibitors combined with lenvatinib and Gemox chemotherapy represent an effective and tolerable regimen for advanced ICC in a multicenter retrospective real-world study. TBS, TNM stage, and PD-L1 expression can be used as potential prognostic factors for OS and PFS.

Development and validation of a selenium metabolism regulators associated prognostic model for hepatocellular carcinoma.

BACKGROUND: Selenium metabolism has been implicated in human health. This study aimed to identify a selenium metabolism regulator-based prognostic signature for hepatocellular carcinoma (HCC) and validate the role of INMT in HCC. METHODS: Transcriptome sequencing data and clinical information related to selenium metabolism regulators in TCGA liver cancer dataset were analysed. Next, a selenium metabolism model was constructed by multiple machine learning algorithms, including univariate, least absolute shrinkage and selection operator, and multivariate Cox regression analyses. Then, the potential of this model for predicting the immune landscape of different risk groups was evaluated. Finally, INMT expression was examined in different datasets. After knockdown of INMT, cell proliferation and colony formation assays were conducted. RESULTS: A selenium metabolism model containing INMT and SEPSECS was established and shown to be an independent predictor of prognosis. The survival time of low-risk patients was significantly longer than that of high-risk patients. These two groups had different immune environments. In different datasets, including TCGA, GEO, and our PUMCH dataset, INMT was significantly downregulated in HCC tissues. Moreover, knockdown of INMT significantly promoted HCC cell proliferation. CONCLUSIONS: The current study established a risk signature of selenium metabolism regulators for predicting the prognosis of HCC patients. INMT was identified as a biomarker for poor prognosis of HCC.

Evolutionary patterns and research frontiers in neoadjuvant immunotherapy: a bibliometric analysis.

Research has shown that neoadjuvant immunotherapy may provide more significant clinical benefits to cancer patients undergoing surgery than adjuvant therapy. This study examines the development of neoadjuvant immunotherapy research using bibliometric analysis. As of 12 February 2023, articles on neoadjuvant immunotherapy in the Web of Science Core Collection were collected. Co-authorship and keyword co-occurrence analyses and visualizations were performed using VOSviewer, while CiteSpace was used to identify bursting keywords and references. The study analyzed a total of 1222 neoadjuvant immunotherapy publications. The top contributors to this field were the United States, China, and Italy, and the journal with the most publications was Frontiers in Oncology. Francesco Montorsi had the highest H-index. The most common keywords were 'immunotherapy' and 'neoadjuvant therapy'. The study conducted a bibliometric analysis of over 20 years of neoadjuvant immunotherapy research, identifying the countries, institutions, authors, journals, and publications involved in this field. The findings provide a comprehensive overview of neoadjuvant immunotherapy research.